Mass spectrometers are widely used in analytical chemistry. Mass analysis of any sample used in a mass spectrometer assumes the production of analyte ions in gas phase or vacuum as a first step. Ion sources of several types have been invented for this purpose. All sample ionization techniques may be divided into two groups: vacuum ionization ion sources and atmospheric pressure ionization sources. The first group includes such techniques as electron impact ionization, fast ion bombardment and secondary ion ionization. A characteristic feature of these ionization sources is that sample ionization occurs inside a mass spectrometer housing under vacuum conditions. The second group, atmospheric pressure ionization sources, includes atmospheric pressure chemical ionization and Electrospray Ionization (ESI). The difference between these two groups of ionization methods is not just quantitative (a value of pressure under which a particular source is operating) but qualitative. First, any atmospheric pressure ionization takes place outside a mass spectrometer instrument. Second, different instrument types are used in both cases. To sample atmospheric pressure ions any mass spectrometer must be equipped with Atmospheric Pressure Interface (API) to transfer ions from an external region of atmospheric pressure to a mass analyzer under high vacuum. Ions produced under atmospheric pressure conditions may be used for other analytical purposes, too. For example, they are used in Ion Mobility Spectroscopy (IMS), which is a fast growing branch of analytical chemistry. Standard IMS instruments operate under pressures close to atmospheric. Thus, only ion sources of the second group (atmospheric pressure ion sources) are used in combination with IMS, because the problem of ion transfer from vacuum to atmosphere against a gas stream has not been solved.
Two major achievements ensure the fast development of modern mass spectroscopy as a powerful tool in analytical chemistry. These are Matrix Assisted Laser Desorption Ionization (MALDI) and Electrospray Ionization (ESI) techniques. Both MALDI and ESI enable the production of intact heavy molecular ions from a condensed phase (solid phase for MALDI and liquid phase for ESI) to be mass analyzed under high vacuum conditions. At the present time, MALDI typically takes place inside a mass spectrometer under high vacuum conditions while ESI is an atmospheric pressure ion source. However, the nature of both MALDI and ESI produced ions is similar. Practical experience shows that these two ionization techniques produce overlapping results sometimes and complimentary in other cases. The advantages of MALDI include simplicity of probe preparation, stability and high tolerance to sample contamination. One of the major advantages of ESI is the atmospheric pressure character of ionization (external with respect to a mass spectrometer), which enables a direct on-line interface with other analytical separation techniques, such as HPLC, CZE, and IMS. An Atmospheric Pressure Interface(API) is used to transfer ions from an atmospheric pressure ion source, such as an ESI, to a vacuum of a mass spectrometer. This interface has an efficiency as low as a few percent. Atmospheric pressure MALDI has not been applied because of the concern that MALDI does not generate enough ions to compensate the loss of ions due to the API.
Recently, Franzen et al. developed a method, disclosed in U.S. Pat. No. 5,663,562, for ionizing heavy analyte molecules deposited on a solid support in a gas at atmospheric pressure. This method comprises two major steps. First, the analyte molecules deposited together with decomposable (explosive) matrix material are blasted into the surrounding gas under atmospheric pressure conditions as a result of decomposition of matrix material under laser irradiation. Neutral gas-phase analyte molecules are produced at this stage. Second, these neutral gas-phase analyte molecules are ionized by atmospheric pressure chemical ionization for further analysis by a mass spectrometer.